Methods and compounds for prevention and treatment of elevated intraocular pressure and related conditions

Abstract

A GPCR-like protein is described, as well as inhibitory/antagonistic compounds and compositions comprising such inhibitors/antagonists of the protein. Such compounds may be used for treating elevated intraocular pressure and conditions associated with elevated intraocular pressure, such as glaucoma.

1 - 22 . (canceled)  
     
     
         23 . A substantially pure polypeptide comprising an amino acid sequence of at least 278 consecutive amino acids of SEQ ID NO: 2.  
     
     
         24 . The polypeptide of  claim 23 , wherein said polypeptide comprises the amino acid sequence of SEQ ID NO: 2.  
     
     
         25 - 27 . (canceled)  
     
     
         28 . A method for identifying a compound for: (i) lowering intraocular pressure in a subject; (ii) treating a condition associated with elevated intraocular pressure; or (iii) both (i) and (ii); said method comprising: (a) providing a cell expressing an R-14; (b) contacting the cell with a test compound; and (c) determining whether R-14 activity is decreased in the presence of said test compound, said decrease in activity being an indication that said compound may be useful for: (i) lowering intraocular pressure in a subject; (ii) treating a condition associated with elevated intraocular pressure; or (iii) both (i) and (ii).  
     
     
         29 . The method of  claim 28  wherein said decrease in activity is an indication that said compound is an R-14 antagonist.  
     
     
         30 . The method of  claim 28 , wherein said R-14 comprises a polypeptide comprising SEQ ID NO: 2, an active fragment thereof, or a sequence substantially identical thereto.  
     
     
         31 . The polypeptide of  claim 23 , wherein said polypeptide comprises an amino acid sequence at least 70% identical to SEQ ID NO: 2.  
     
     
         32 . The polypeptide of  claim 23 , wherein said polypeptide comprises an amino acid sequence at least 90% identical to SEQ ID NO: 2.  
     
     
         33 . The polypeptide of  claim 23 , wherein said polypeptide comprises an amino acid sequence at least 95% identical to SEQ ID NO: 2.  
     
     
         34 . An isolated nucleic acid encoding the polypeptide of  claim 23 .  
     
     
         35 . The isolated nucleic acid of  claim 34 , wherein said nucleic acid comprises a nucleotide sequence at least 70% identical to SEQ ID NO: 1.  
     
     
         36 . The isolated nucleic acid of  claim 34 , wherein said nucleic acid comprises a nucleotide sequence at least 90% identical to SEQ ID NO: 1.  
     
     
         37 . The isolated nucleic acid of  claim 34 , wherein said nucleic acid comprises a nucleotide sequence at least 95% identical to SEQ ID NO: 1.  
     
     
         38 . The isolated nucleic acid of  claim 34 , wherein said nucleic acid comprises the nucleotide sequence of SEQ ID NO: 1.  
     
     
         39 . An isolated nucleic acid comprising a nucleotide sequence complementary to a nucleotide sequence encoding the polypeptide of  claim 23 .  
     
     
         40 . The isolated nucleic acid of  claim 34 , wherein said nucleic acid comprises a nucleotide sequence that hybridizes under moderately stringent conditions to a nucleic acid consisting of the nucleotide sequence of SEQ ID NO: 1, or the complement thereof.  
     
     
         41 . The isolated nucleic acid of  claim 34 , wherein said nucleic acid comprises a nucleotide sequence that hybridizes under stringent conditions to a nucleic acid consisting of the nucleotide sequence of SEQ ID NO: 1, or the complement thereof.  
     
     
         42 . A recombinant nucleic acid comprising the nucleic acid of  claim 34  operably linked to a transcriptional regulatory element.  
     
     
         43 . A vector comprising the recombinant nucleic acid of  claim 42  suitable for introduction into a host cell.  
     
     
         44 . A host cell comprising the recombinant nucleic acid of  claim 42 .  
     
     
         45 . The host cell of  claim 44 , wherein the recombinant nucleic acid is integrated into a chromosome of the host cell.  
     
     
         46 . The host cell of  claim 44 , wherein the cell is a eukaryotic or prokaryotic cell.  
     
     
         47 . A method of producing a substantially pure polypeptide comprising an amino acid sequence of at least 278 consecutive amino acids of SEQ ID NO: 2, the method comprising culturing the host cell of  claim 44  under conditions permitting the expression of said substantially pure polypeptide.  
     
     
         48 . A method of lowering intraocular pressure or treating a condition associated with elevated intraocular pressure in a subject, said method comprising administering to said subject an effective amount of a compound that is an antagonist of a polypeptide comprising SEQ ID NO: 2.  
     
     
         49 . The method of  claim 49  wherein said subject suffers from glaucoma.